Poster Sessions

DEV-3

John Thomas

J. Thomas, P. Canelos, F. Luyten, M. Moos, Jr

XSMOC-1 Inhibits BMP Signaling and Is Essential for Post-Gastrulation Development in Xenopus

Biochemical purification of highly-purified fractions of bovine cartilage, containing potent bone forming activity, was found to contain Secreted Modular Calcium-Binding Protein-2 (SMOC-2). Data regarding the biological function of this BM-40 family member and the closely related SMOC-1 remain limited. Furthermore, their expression or function during embryological development is unknown. We isolated the Xenopus ortholog of human SMOC-1 (XSMOC-1) and explored its function in Xenopus embryos. XSMOC-1 expression could first be detected anteriorly at stage 12.5, at the end of gastrulation and onset of neurulation. Gain-of-function assays demonstrated XSMOC-1 acts as an antagonist of Bone Morphogenetic Protein (BMP) activity. However, in contrast to known extracellular ligand-binding BMP antagonists, such as Noggin, SMOC inhibits BMP activity downstream of the receptor. Evidence is provided to suggest SMOC acts via activation of MAP-kinase signaling resulting in phosphorylation of the linker region of Smad 1, 5, 8. Loss-of-function studies demonstrated a catastrophic developmental failure of post-gastrulation development in the absence of XSMOC-1. These findings provide the first evidence of the importance of the SMOC family of proteins during embryological development.